This proposal is for a five year renewal (years 11 through 15) of the Alzheimer's Disease Cooperative Study (ADCS). This consortium of 34 academic medical centers and 65 participating sites is proposing to continue to carry out clinical drug trials for promising to continue to carry out clinical drug trials for promising new agents designed to ameliorate behavioral symptoms, improve cognition, slow the rate of decline or delay the appearance of Alzheimer's disease (AD). We will also expand our efforts in the recruitment of minority groups into AD clinical trials. Development of instruments will now shift to developing instruments suitable for data collection in primary prevention trials where data can be collected efficiently in a subjects home and returned by mail with minimal use of interviewer time, allowing for cost-effective, large prevention trials. Subjects in our trials will range from normal individuals to individuals with moderate dementia. Trials will range in size from small 1A trials involving 15 subjects to a very large primary prevention trials with a planned enrollment of 2,700 normal elderly. As a follow-up to our previous vitamin E trial and ongoing MCI trial, we are proposing a primary prevention trial to test the theory that the use of cellular and mitochondrial antioxidants, both alone and in combination, will prevent the development of AD in normal elderly. Our new protocols will also include the development of two new molecules (a neuroactive peptide [NAP] and indole-3 propionic acid [IPA], a potential anti-oxidant) that will be tested in Phase 1 trials. We will also test a combination of vitamins (folate/B6/B12) that have been demonstrated to reduce homocysteine levels, a risk factor for AD on the theory that this will lead to a slowing in the rate of decline. A trial of a drug designed to lower cholesterol will follow up on new data suggesting that lower cholesterol decreases the deposition of beta amyloid. We also are including a new trial design employing divalproex sodium to block the emergence of behavioral symptomatology.